+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Structural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemia.

      Proceedings of the National Academy of Sciences of the United States of America
      Albumins, metabolism, Binding Sites, Humans, Hyperthyroxinemia, genetics, Models, Molecular, Molecular Structure, Protein Binding, Thyroxine, X-Ray Diffraction

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Human serum albumin (HSA) is the major protein component of blood plasma and serves as a transporter for thyroxine and other hydrophobic compounds such as fatty acids and bilirubin. We report here a structural characterization of HSA-thyroxine interactions. Using crystallographic analyses we have identified four binding sites for thyroxine on HSA distributed in subdomains IIA, IIIA, and IIIB. Mutation of residue R218 within subdomain IIA greatly enhances the affinity for thyroxine and causes the elevated serum thyroxine levels associated with familial dysalbuminemic hyperthyroxinemia (FDH). Structural analysis of two FDH mutants of HSA (R218H and R218P) shows that this effect arises because substitution of R218, which contacts the hormone bound in subdomain IIA, produces localized conformational changes to relax steric restrictions on thyroxine binding at this site. We have also found that, although fatty acid binding competes with thyroxine at all four sites, it induces conformational changes that create a fifth hormone-binding site in the cleft between domains I and III, at least 9 A from R218. These structural observations are consistent with binding data showing that HSA retains a high-affinity site for thyroxine in the presence of excess fatty acid that is insensitive to FDH mutations.

          Related collections

          Author and article information


          Albumins,metabolism,Binding Sites,Humans,Hyperthyroxinemia,genetics,Models, Molecular,Molecular Structure,Protein Binding,Thyroxine,X-Ray Diffraction


          Comment on this article